Synthesis of halohydrins from epoxides using quaternized amino functionalized cross-linked polyacrylamide as a new solid–liquid phase transfer catalyst

Reactive & Functional Polymers 51 (2002) 7–13 www.elsevier.com / locate / react

Synthesis of halohydrins from epoxides using quaternized amino functionalized cross-linked polyacrylamide as a new solid–liquid phase transfer catalyst B. Tamami*, H. Mahdavi Chemistry Department, Shiraz University, Shiraz, Iran Received 1 May 2001; received in revised form 26 September 2001; accepted 13 October 2001

Abstract Poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide resin was developed as new solid–liquid phase transfer catalyst. This quaternized polyacrylamide-catalyzed regioselective ring opening of epoxide by halides (F, Cl, Br, I), to give halohydrins in high yield under mild conditions.  2002 Elsevier Science B.V. All rights reserved. Keywords: Polyacrylamide; Phase transfer catalyst; Halohydrin; Epoxide; Quaternization

1. Introduction Phase-transfer catalysts (PTC) facilitate reactions between water-soluble reagents and organic soluble substrates. The most important PTCs, which have been used widely in organic reactions, are quaternary ammonium and phosphonium salts, crown ethers, and cryptands [1– 3]. These catalysts are generally not recovered and this is a problem when the relatively expensive cryptands and crown ethers are used. On the other hand, some of the ammonium and phosphonium salts sometimes form stable emulsions. During the last decades much interest has been focused on the applications of functionalized polymers as phase transfer catalysts [4,5], *Corresponding author. Fax: 1 98-71-200-27. E-mail address: [email protected] (B. Tamami).

because they provide great ease in separation of the catalyst and isolation of the product. A significant number of quaternary ammonium and phosphonium salts as well as crown ethers and cryptands bound to polystyrene type resins have been used in synthetic organic chemistry [4–8]. Polyacrylamide and its modified forms have been used as cosolvent-type catalysts for nucleophilic displacement reactions under biphase and triphase conditions [9], as support for the solid phase synthesis of peptides [10], for metal complexion [11,12], and for the preparation of a number of polymer-supported reagents [13–15]. These supported systems, were found to have entirely different characteristics in terms of polarity, solvation, and reactivity compared to commonly used polystyrene-supported species. Epoxides are important intermediates in or-

1381-5148 / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved. PII: S1381-5148( 01 )00119-5

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ganic synthesis [16]. No reaction of epoxides has more thoroughly been studied and widely used in organic synthesis than the addition of nucleophilic agents to epoxides to form 1,2disubstituted products [17,18]. Synthesis of halohydrins from epoxides have been a subject of much interest [17,19–21], in particular special attention has been paid on the ring-opening of epoxides to give fluorohydrin as a method for the introduction of a fluorine atom into organic molecules [22]. In addition there are a number of reports on the ring opening reactions of epoxides under phase-transfer condition [23]. As far as we know there has been no report in the literature on the use of modified polyacrylamide as polymeric phase transfer catalyst in organic reactions. Here we report the preparation and use of a quaternized amino functionalized cross-linked polyacrylamide as an efficient heterogeneous phase-transfer catalyst in conversion of epoxides to their halohydrins. 2. Experimental

2.1. Material and technique Acrylamide (Fluka) was recrystallized from chloroform. Divinylbenzene (55%) (Fluka) was washed with sodium hydroxide solution (1%, 10 ml 3 2) and water (20 ml 3 3), to remove the inhibitor. Benzoyl peroxide (Fluka) was purified [24]. Other reagents and solvents were used without further purification. Gas chromatography was recorded on a Shimadzu GC 14-A. IR spectra were run on a Perkin-Elmer IR-157G Spectrophotometer. NMR spectra were recorded on a Bruker Avance DPX instrument (250 MHz). All products characterized by comparison of their IR and NMR spectra and physical data with those of the authentic samples. All yields refer to the isolated products.

2.2. Preparation of cross-linked polyacrylamide Divinylbenzene (3.9 g, 0.03 mol) and acrylamide (60.4 g, 0.85 mol) were dissolved in

ethanol (250 ml). Benzoyl peroxide (350 mg, 1.4 mmol) was added and the mixture was heated while stirring at 70–75 8C, for 5 h. The polymer formed was collected by filtration, washed several times with water, ethanol, benzene, and tetrahydrofuran, and dried at 60 8C under reduced pressure. The IR spectrum of the polymer showed the characteristic absorption of amide (N–H) at 3200 and 3300 cm 21 , and carbonyl groups at 1660 cm 21 .

2.3. Preparation of poly[ N-(2 aminoethyl)acrylamide] Polyacrylamide (10 g) was equilibrated with excess ethylenediamine (100 ml) for 12 h, and then the mixture was heated at 100 8C for 12 h while stirred. The reaction mixture was poured into cold water (1 l). The resin was filtered and washed with NaCl solution (0.1 M) until the filtrate was free from ethylenediamine, as indicated by the absence of blue coloration with ninhydrin reagent. The gel was washed with o water, methanol and then dried at 60 C under reduced pressure. The IR spectrum of the amino functionalized polyacrylamide showed the characteristic absorption of amino (N–H) group at 3500 cm 21 . The amino group content was determined by back titration and was found to be equal to 3.72 mmol / g.

2.4. Preparation of poly[ N-(2 aminoethyl)acrylamido] trimethyl ammonium iodide resin Poly[N-(2-aminoethyl)acrylamide] (5 g) was equilibrated in DMF (100 ml) for 12 h. Methyl iodide (20 ml, 320 mmol) and NaOH (1 g, 25 mmol) was added and the reaction mixture stirred at room temperature for 48 h. The quaternized polymer was collected by filtration, washed several times with water, methanol until the filtrate was free from CH 3 I, as indicated by absence of formation of AgI with AgNO 3 . Finally the polymer was washed with ether and dried at 50 8C under reduced pressure. Yield 5 8.23 g. The capacity of quaternized resin was

B. Tamami, H. Mahdavi / Reactive & Functional Polymers 51 (2002) 7 – 13

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determined both gravimetrically and by titration method. This was found to be 3.21 and 3.06 mmol / g of resin, respectively. For conversion of iodide form of resin to other halide forms, the resin (5 g) was added to the metal halide aqueous solution (2 M, 100 ml), and the mixture was stirred for 12 h. The polymer sample was filtered, washed successfully with distilled water, ether and dried at 50 8C under reduced pressure.

2.5. Typical procedure for the reaction of epoxide with metal halides under PTC To a mixture of epoxide (1.0 mmol) and metal halide (5 mmol) (M 5 Na, K and X 5 F, Cl, Br, I) in a CH 3 CN (10 ml) was added Poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide ( | 0.1 g). The suspension was stirred at room temperature for the lengths of time shown in Table 2. Progress of each reaction was monitored by TLC, using CCl 4 – ether (5:1) as eluent and / or GC. Polymer and salt were removed by filtration. The organic solvent dried with anhydrous Na 2 SO 4 . The corresponding pure product was obtained upon evaporation of solvent. The characterization of 1 13 product was performed with H and C NMR, and IR techniques. The reaction could also be carried out in water. In this case, after filtration, the products were obtained upon extraction with CH 2 Cl 2 and evaporation of the solvent.

3. Results and discussion Polyacrylamide cross-linked with divinylbenzene (2%) was prepared by free radical solution polymerization of the monomer mixture in ethanol using benzoylperoxide as initiator [14]. The resulting polymer was characterized by IR spectroscopy. The IR spectrum showed peaks at 3500 cm 21 (N–H amide), 1660 cm 21 (C=O amide), and 800 cm 21 (aryl group). Poly[N-(2aminoethyl)acrylamide] was obtained by transamidation reaction of cross-linked poly-

Scheme 1.

acrylamide with excess amount of ethylenediamine (Scheme 1). The amino resin was characterized by IR spectroscopy, and semiquantitative ninhydrin reaction [25]. The resin gave a deep blue colour on heating with ninhydrin reagent. The amino group capacity of the resin was determined by alkalimetric method to be 3.72 mmol / g of resin. Poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium iodide was prepared by the reaction of poly[N-(2-aminoethyl)acrylamide] with excess of methyl iodide in DMF at room temperature (Scheme 1). The resulting quaternized polymer was characterized by IR spectroscopy. The IR spectrom showed peak at 1660 cm 21 (C=O, amide) and the intensity of the broad bond of N–H starching was reduced considerably. The capacity of quaternized resin was determined gravimetrically and by titration method to be 3.21 and 3.06 mmol / g of resin, respectively. The synthetic utility of this modified polymer was explored by examining the reaction of epoxides with metal halide (MX, M 5 Na, K and X 5 F, Cl, Br, I) for preparation of halohydrins using the polymer as a phase transfer catalyst. The effects of solvent and molar ratio of the polymer on the ring opening reaction of epoxides were investigated. The reactions were carried out in different wet solvents such as tetrahydrofuran, chloroform, dichloromethane, ethylacetate, water, and acetonitrile. The last two solvents proved to be the best (Table 1). The optimum molar ratio of the

B. Tamami, H. Mahdavi / Reactive & Functional Polymers 51 (2002) 7 – 13

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Table 1 The effect of solvent on reaction of styrene oxide with NaBr using the polymeric PTC a Entry

Solvent

Time (h)

Conversion (%)

1 2 3 4 5 6

THF CHCl 3 CH 2 Cl 2 CH 3 COOC 2 H 5 H2O CH 3 CN

4 4 4 4 4 1

10 0 0 6 100 100

a The molar ratio of the polymeric catalyst to styrene oxide 0.2:1.

polymeric catalyst to epoxide was found to be 0.2:1. The reactions of different epoxide with halides were performed effectively and in high yields (Table 2, Scheme 2). The experimental results showed that, water can also be used as solvent in this reaction, except that in comparison to acetonitrile, the time of reaction was longer. Except for the reaction of styrene oxide (Table 2, entries 1–4) and 1,2-hexene oxide (Table 2, entries 21–24) which produce small percentage of the other regio isomer, the reaction of other epoxides were found to be highly regioselective and only one isomer was obtained. The observed regioselectivity and formation of trans products for reaction of cyclohexene oxide clearly indicates that the reaction proceeds through an S N 2 type mechanism. It is interesting to point out that, the ring opening of epoxides to give fluorohydrins have been carried out with different reagents such as, hydrogen fluoride [22b], potassium hydrogen difluoride [22c,d], pyridine polyhydrofluoride [22e], silicon tetrafluoride [22f], etc., as methods for introducing the fluorine atom into organic molecules. However the use of anhydrous hydrogen fluoride and its modified forms in most cases require heating at high temperatures for long periods which often cause by products resulting from rearrangements, polymerization, or hydrofluorination of double bonds and thus

decreasing regioselectivities [22g]. The present fluorohydrin formation from epoxides mediated by poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide resin as PTC has the following advantages over the existing methodologies: the reaction can be operated under mild conditions for a short period of time at low temperature with high regioselectivity and also ease of work up and separation of product. In order to get an insight into the role of the poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide resin as a polymeric phase transfer catalyst, a series of reactions were performed on styrene oxide with NaBr under different conditions (Table 3). Obviously, in the absence of the catalyst no reaction occurred. Also in the presence of poly[N-(2-aminoethyl)acrylamide] or polyacrylamide the reaction did not proceed. This could that, as it was obvious, the presence of a quaternary site is necessary for the polymer to act as a phase transfer catalyst. However, surprisingly the reaction was extremely slow when the monomeric catalyst such as tetrabutylammonium bromide or Amberlyst A-26 Br 2 form were used (entries 4–6). These experimental facts let us to believe that poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide resin acts both as a catalyst for nucleophilic ring opening reaction as well as a phase transfer agent. Even combination of poly[N-(2-aminoethyl)acrylamide] and tetrabutylammonium bromide (entry 8) were unsuccessful and the reaction proceeded with very low conversion. It seems that the polymeric catalyst carrying the nucleophile has strong attracting efficiency for the epoxy substrate and the reaction proceeds smoothly in the vicinity of the catalyst. Probably the ring opening of the epoxy molecule is catalyzed by hydrogen bonding between the oxygen of the epoxy molecule and amidic hydrogen of the polymer. This is supported by the experimental facts (entry 7) that the presence of an amidic group as well as the quaternary site on the polymeric catalyst is necessary for the reaction to proceed with a complete conversion.

B. Tamami, H. Mahdavi / Reactive & Functional Polymers 51 (2002) 7 – 13

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Table 2 Reaction of epoxides with MX in presence of 0.2 mol equivalent of poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium chloride resin as PTC a Entry

Yield (%)c

Solvent

1 2 3

NaF KCl NaBr NaBr

CH 3 CN CH 3 CN H2O CH 3 CN

1 1 4 1.5

19: X 5 F 29: X 5 Cl 39: X 5 Br

93 d (91,9)e 91 d (90,10)e 92 d (92,8)e 91 d (91,9)e

4

KI KI

H2O CH 3 CN

6 1.5

49: X 5 I

93 d (90,10)e 92 d (91,9)e

5 6 7

NaF KCl NaBr NaBr KI KI

CH 3 CN CH 3 CN H2O CH 3 CN H2O CH 3 CN

1.1 1 6 1.5 6 2

59: X 5 F 69: X 5 Cl 79: X 5 Br

94 92 91 92 92 91

9 10 11 12

NaF KCl NaBr KI

CH 3 CN CH 3 CN H2O H2O

1 1 7 10

99: X 5 F 109: X 5 Cl 119: X 5 Br 129: X 5 I

94 90 89 90

13 14

NaF KCl

CH 3 CN CH 3 CN

1 1

139: X 5 F 149: X 5 Cl

92 89

15

NaBr NaBr KI KI

H2O CH 3 CN H2O CH 3 CN

6.5 2 8 2.5

159: X 5 Br

90 91 91 90

17 18 19 20

NaF KCl NaBr KI

CH 3 CN CH 3 CN H2O H2O

10 10 10 7

179: X 5 F 189: X 5 Cl 199: X 5 Br 209: X 5 I

0 20 87 90

21 22 23

NaF KCl NaBr

CH 3 CN CH 3 CN H2O

1 1 10

219: X 5 F 229: X 5 Cl 239: X 5 Br

90 (84,16) 89 d (87,13)e 89 d (84,16)e

24

KI

H2O

8

259: X 5 I

88 (82,18)

25 26 27 28

NaF KCl NaBr KI

CH 3 CN CH 3 CN CH 3 CN CH 3 CN

1 1 10 11

269: X 5 F 279: X 5 Cl 289: X 5 Br 299: X 5 I

91 90 91 93

29

NaF

CH 3 CN

3

139: X 5 F

78

16

Time (h)

Product b

MX

8

Epoxide

89: X 5 I

169: X 5 I

d

d

e

e

B. Tamami, H. Mahdavi / Reactive & Functional Polymers 51 (2002) 7 – 13

12 Table 2. Continued Entry

Epoxide

Time (h)

Product b

Yield (%)c

MX

Solvent

30

KCl

CH 3 CN

3

149: X 5 Cl

81

31

NaBr

CH 3 CN

12

159: X 5 Br

87

32

KI

CH 3 CN

10

169: X 5 I

89

33 34 35 36

NaF KCl NaBr KI

CH 3 CN CH 3 CN CH 3 CN CH 3 CN

10 10 8 6

339: X 5 F 349: X 5 Cl 359: X 5 Br 369: X 5 I

0 30 90 89

a

All of the reactions were carried out at room temperature. Products were identified by comparison of their IR and NMR spectra and / or physical data with the authentic samples. c Yield refers to isolated product. d Two regio-isomers were obtained and yield refers to both of isomers. e Less hindered side regio isomer was obtained in higher yield. b

resin proved to be a highly efficient polymeric phase transfer catalyst for regioselective ring opening of epoxides to halohydrins by halide anions. It played a special role as an electrophilic catalyst, as well, for such reactions. The resin has the inherent advantages of a solid phase transfer catalyst, including operational simplicity, filterability, regenerability, and reuse. In addition another advantage of this system is to provide a single method for preparation of all four halohydrins from cheap metal halides. Reactions of epoxides with other nucleophiles under phase transfer conditions using this polymer and the effect of parameters such as the nature of alkyl groups on the quaternized site

Scheme 2.

As seen in experimental parts, workup of the reaction was very easy and pure products were isolated without any purification. The filtered polymeric catalyst could be recovered several times and used without any lose in its capacity and efficiency. In conclusion poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide

Table 3 The reaction of styrene oxide with NaBr a Entry

Solvent

Catalyst

1 2 3 4 5 6 7 8

CH 3 CN CH 3 CN CH 3 CN CH 3 CN CH 3 CN CH 3 CN CH 3 CN CH 3 CN

– A B C D D E A1C

a

b

Time (h)

Temp. (8C)

Conversion (%)

18 6 6 18 18 2 1.5 18

25 25 25 25 25 Reflux 25 25

0 0 0 2 5 5 100 10

The mole ratio of catalyst to epoxide was 0.2. The type of catalysts were: (A) poly[N-(2-aminoethyl)acrylamide]; (B) polyacrylamide; (C) tetrabutyl ammonium bromide; (D) amberlyst A26; (E) poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium bromide. b

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